This proposal represents the doctoral work of Peter A. Garrett, M.D. Dr. Barbara S. Hulka is Dr. Garrett's dissertation supervisor and will serve as the principal investigator. This proposed case-control study will evaluate the hypothesis that individuals with unusual sequence lengths of the variable tandem repeat region of the Ha-ras proto oncogene have an increased susceptibility to breast cancer. Possible confounding and modifying effects of previously known or suspected risk factors for breast cancer will also be considered. It is planned that 150 female breast cancer patients and 150 suitable female controls will be enrolled from three local hospital clinics over a one year period. An in-person questionnaire will be administered and a sample of peripheral blood will be obtained from each participant before discharge from the clinic. DNA will be extracted from peripheral leukocytes and assayed for Ha-ras polymorphisms by the Southern blot technique. Statistical analyses will be performed to determine the association between rare Ha-ras alleles and breast cancer, while assessing possible confounding and modifying effects of traditional beast cancer risk factors. Results of this study will be of both theoretical and clinical importance: A positive association will provide new information regarding the biology and etiology of breast cancer. Additionally, Ha- ras polymorphism status might present itself as a new biological marker in the identification of high risk individuals and families for more intensive surveillance.